Despite the development of advanced methods of nutritional support and therapy, malnutrition in cancer patients remains a serious and frequent problem. In 1986, Tchekmedyian et.al. observed weight gain in 30 of 33 advanced breast cancer patients treated with megestrol acetate, a progestational steroid. Another group has observed weight gain in 13 of 14 AIDS patients treated with megestrol acetate. Preliminary data obtained recently by our group demonstrate increased food intake, weight gain and increased body fat in patients with advanced lung cancer treated with megestrol acetate. Megestrol acetate may be causing weight gain by one or a combination of three mechanisms: increased food intake,decreased energy expenditure, or fluid retention. Progesterone treatment of rats has demonstrated weight gain with constant food intake, and studies of megestrol acetate in vitro suggest it may act directly on the adipocyte to affect the balance of triglyceride synthesis and breakdown. We propose to study patients with stage III non-small cell lung cancer randomly assigned to receive placebo or megestrol acetate over an 8 week period. We plan to measure food intake using dietary records, and energy expenditure both at rest by indirect calorimetry under controlled metabolic ward conditions and in ambulatory patients using the doubly labelled water method. Lean body mass will be measured by total body (40)K counting and body water will be measured using doubly labelled water under metabolic ward conditions during the first,fourth and eighth week of treatment with megestrol acetate or placebo. Studies will be carefully coordinated with the treatment of patients and clinical outcome data collected. Fat biopsies will be performed under controlled conditions to obtain measurements of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) catalytic activity, LPL immunoreactive mass, fat cell size, fat cell number and HSL and LPL m-RNA content. These studies should provide critical information in understanding the action of this promising new approach to this important clinical problem.